Embryo Transfer & Embryo Implantation
Embryo Transfer & Embryo Implantation is most often done on an outpatient basis & No anesthesia is used. The enigma of embryo implantation - why doesn't every embryo become a baby?
Test Tube Babies - IVF & GIFT (Page 3)From the book
How to Have a Baby: Overcoming Infertilityby Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
Embryo transfer is most often done on an outpatient basis. No anesthesia is used, although some women may wish to have a mild sedative. The patient lies on a table or bed, usually with her feet in stirrups.. Using a vaginal speculum, the doctor exposes the cervix. One or more embryos suspended in a drop of culture medium are drawn into a transfer catheter, a long, thin sterile tube with a syringe on one end. Gently, the doctor guides the tip of the loaded catheter through the cervix and deposits the fluid containing the embryos into the uterine cavity. The procedure should be done with great care and usually takes between 10 and 20 minutes. Some doctors perform the transfer under ultrasound guidance, to ensure proper placement of the embryos in the uterine cavity. Most doctors advise a few hours of bed rest after the transfer.
Fig 1. Ultrasound guided embryo transfer. The air bubble echo confirms accurate placement of the catheter in the uterine cavity
Most clinics today transfer 2-3 good quality embryos on Day 2 or Day 3.
Fig 2. 3 Grade A embryos . These have 2-cells, 4-cells and 8-cells respectively
Embryos are graded according to their appearance and rate of cell-division and good quality embryos are those which have 4-8 cells, of equal size, with clear cytoplasm, and with few fragments. These are called Grade A embryos. Embryos with more fragments are assigned a lower grade, and they usually have a lower chance of implanting . However, the babies which result from these embryos are completely normal, if they do implant successfully.
Please insist that your clinic give you photos of your embryos. This is invaluable documentation and will help to ensure that you have received good quality care. Good clinics do this routinely. All well -equipped clinics have the facilities to provide you with photos of your embryos. If your doctor refuses to provide these photos, you should be very concerned as to the quality of care you are getting.
Some times, only embryos of poor quality are available for transfer. While the chance of getting pregnant when only poor quality embryos are transferred, you can be reassured that if a pregnancy results, the children will be normal !
How many embryos to transfer is one of the most difficult decisions facing an IVF patient today. The more the embryos transferred, the greater the chances of getting pregnant. Since the purpose of an IVF cycle is to achieve a pregnancy, then why not transfer as many as possible? However, the price you pay for transferring more embryos is that the risk of a multiple pregnancy increases as well.
In some countries, such as the UK, doctors are allowed to replace a maximum of only 2 embryos, to reduce the risk of high-order multiple births. Some clinics in Scandinavia have now started transferring only one embryo ( this is called SET or single embryo transfer) in young women, in order to reduce the risk of a multiple pregnancy. In USA and India, there are no laws, and some clinics will transfer 4 embryos for young patients, and upto 6 for older women - and this number is quite arbitrary.
Doctors have tried to develop an embryo score ( based on the number of embryos and embryo quality ) in order to predict the chances of a pregnancy after embryo transfer, but this is still not precise. I always tell patients that if IVF technology was perfect, and if every embryo became a baby, we would transfer only one embryo, and I wouldn't need to discuss this with them. Since the technology is still not perfect, and we still cannot predict which embryo will become a baby, there is no easy answer as to how many embryos to transfer. This is why many clinics will allow patients to decide for themselves. This is always a difficult decision, and you need to carefully weigh the pros and cons before making up your mind. There is no right or wrong number - and you need to take the path of least regret.
Transferring more embryos increases the chances of getting pregnant, and also increases the risk of a multiple pregnancy. However, a high-order pregnancy is a complication for which the doctor can perform a selective fetal reduction, in order to reduce this to twins. Not getting pregnant may be a worse outcome for some patients! If embryo freezing facilities are available, then supernumerary embryos can be stored, and this needs to be factored in as well.
The terrible 2ww - 2 week wait !
The embryo transfer completes the medical treatment in the IVF cycle and most clinics provide "luteal phase support" after the transfer , usually with estrogen tablets and progesterone suppositories, to increase the chances of implantation. However, this period is often the hardest part of an IVF cycle for the patient, because of the agony and suspense of waiting to find out if a pregnancy has occurred. This can be determined by a blood test , which measures the level of the hormone, HCG ( human chorionic gonadotropin) only 10 to 14 days after the transfer. For many patients, these 14 days are often the longest days of their life !
A positive beta HCG level ( of more than 10 miU/ml) means you are pregnant, and the doctor will then monitor your pregnancy to confirm it is healthy; intrauterine; and to check how many embryos have implanted.
It is normal to blame yourself for something you may or may not have done during this time if you do not conceive. Therefore, try not to do anything for which you will blame yourself if you do not get pregnant. In general the following guidelines are offered:
- No tub baths or swimming for 48 hours after replacement
- No douching or tampons
- No intercourse or orgasms until the fetal heartbeat is seen on ultrasound, or the pregnancy test is negative
- Do not undertake excessive physical activity such as jogging, aerobics, or tennis
- No heavy lifting
- You may return to "work" after 24 hours of bed rest (getting up for bathroom and meals only) and one to two days of light activity.
It's safe to travel 2-3 days after the transfer.
If you are unsure whether or not to do something, take the "path of least regret". Ask yourself - if I don't get pregnant, will I blame myself for doing this ? And if the answer is yes, don't do it !
You may have some vaginal spotting or bleeding prior to your blood test. However, you must have the blood test done, even if you think your period has started. There are no symptoms or signs which will be able to tell you whether or not you are pregnant.
Many doctors used to advise "strict bed rest" after an embryo transfer. However, remember that your physical activity does not affect your chances of getting pregnant. Resting when you are well can be very emotionally taxing, and we encourage patients to lead as normal a life as possible. Many patients are worried that if they cough or sneeze , the embryo will "fall out". However, remember that this is physically impossible, and that if the embryo is going to implant, it will, no matter how much you exert physically. Remember that God has designed the human body with enough sense, that coughing and sneezing will not cause the embryos to "fall out". The uterine cavity is a "potential space", and once the embryos are placed here, they appose to the uterine wall and are not affect by gravitational forces. I remind patients that it's fine for them to do whatever normal couples would do after having sex - after all, how does it matter to the embryo that it arrives in the uterine cavity in the normal course of events, after the couple had sex, or after spending 2 days in the IVF laboratory and then being transferred into the cavity with a catheter ?
Thus, there are numerous stages to every IVF treatment cycle, each of which must be reached and completed before moving on to the next stage:
- more than one should egg develop
- eggs should mature
- ovulation should not occur before the eggs can be collected
- eggs must be retrieved during the "pick-up"
- sperm must fertilize at least one egg
- fertilized eggs must divide and grow healthily,... and all this so that...
- the embryos might get implanted in the uterus
Think of it as a series of hurdles, all of which have to be cleared , in order to win the race !
The enigma of embryo implantation - why doesn't every embryo become a baby?
While modern technology is very good at making embryos in the laboratory, we still cannot control the implantation process. We do not know which embryo will become a baby - and this can be very frustrating, for both patients and doctors ! Many patients who do not get pregnant after an embryo transfer start believing that their bodies are defective, and that they have "rejected" the embryo. They feel that if they failed to become pregnant even after the doctor transferred 3-4 good quality embryos, that they are flawed. However, you need to remember that embryo implantation is a very complex process, which consists of a series of phases in which the embryo has to appose and attach itself to the maternal endometrium and invade into it.
First, the embryo has to undergo further development, till it reaches the blastocyst stage, when it hatches from its shell, known as the zona.
Fig 3. Hatched blastocyst.
The hatched blastocyst then needs to implant in the endometrium, and the three phases of implantation are known as apposition, adhesion and invasion, and occur during the period of time known as the implantation window. Apposition, or orientation of the embryo (which is at the blastocyst stage at this time ) within the cavity of the uterus, starts when the cavity has become minimal due to the suction of endometrial fluid by pynopods (small protrusions found on the surface membrane of the cells lining the uterus). Adhesion of the blastocyst is a progressive phenomenon that ties the embryo to the endometrium and is the primary event initiating invasion. Many molecules, such as cytokines, growth factors and cell adhesion proteins called integrins play an important role in this complex process during which the blastocyst and maternal endometrium must undergo an exquisite dialogue. Invasion is a self-controlled proteolytic process that allows the embryonic trophoblast to penetrate deep into the maternal decidua and to invade the endometrial spiral arteries by producing chemicals called proteinases. How implantation is regulated and brought about remains an enigma, but we need to remember that the implantation process is surprisingly inefficient in humans - Nature is not always very competent! After IVF, it's only about 10%, which means that only 10% of embryos implant successfully to become a baby.
The responsibility for this low efficiency has to be shared between the embryo as well as a defective embryo-endometrium dialogue. We still cannot successfully predict which patient will get pregnant after embryo transfer . We now know that one of the major reasons for failure of the embryo to implant is a genetically abnormal embryo. Basic research on implantation is of great interest today, because embryonic implantation is the major factor limiting in allowing pregnancy after ART, but we still need to learn a lot about this "black hole" in our knowledge, before we can learn to control it !
Many patients blame themselves when they don't get pregnant after an embryo transfer. They feel that the fact that the embryo did not implant means either that their body is defective; or that it "rejected" the embryo; or that they did not rest enough. However, please do remember that embryo implantation is a complex process, which you cannot influence by your diet or physical activity - so there is no need for you to blame yourself if the embryos do not implant.
Maximizing Chances For Success
- Avoid all unnecessary medications other than paracetamol ( Tylenol) . If you are taking other prescription medications check with us prior to beginning your treatment cycle.However, if you do need to take meds, please do so - they do not have any adverse influence on the embryos we have transferred. The restrictions on taking medications during pregnancy only apply after the HCG test is positive - not before that. This is because your embryos have still not established a blood supply from you, which means even if you do take meds, these will not harm the embryos as they will not be able to reach them in a sufficient concentration.
- No smoking or alcohol use. Studies show both can result in lower pregnancy rates and a greater risk of miscarriage. Why put yourself through this if you are not doing everything YOU can to insure your success.
- No more than two caffeinated beverages per day.
- Avoid change in diet or weight loss or fad diets during IVF cycle. A healthy well balanced diet works best.
- Refrain from intercourse following embryo replacement until the pregnancy test is done .
- Normal exercise may continue unless enlargement of your ovaries produces discomfort.
- Avoid hot tubs or saunas.
- Fever greater than 100.4 C one to two months prior to IVF treatment may adversely effect sperm quality. Be sure to let us know. If you are sick, please take your temperature and report any febrile illnesses.
- Sitting in hot tubs and saunas is not recommended. Please refrain from this for at least three months prior to treatment.
- Drugs, alcohol, and cigarette smoking should be avoided for three months prior to treatment and at all times during the ongoing IVF treatment cycle to get the best results.
- Abstain from intercourse for at least three days, but not more than seven days prior to collection of semen for egg collection and during treatment.
The Cost of IVF
The cost of a single IVF treatment cycle in our clinic is US $ 4000. However, this cost varies from clinic to clinic, depending on the program and the items included in the fee. It is important to get an itemized listing from the selected program of what costs are included in the treatment cycle. Try to find your "total" medical cost - how much you will have to spend out of your own pocket for the entire treatment. Many clinics do not include the cost of certain procedures ( such as ultrasound scans) and these can then add up to quite a bit ! Other expenses to be aware of include time missed from work and travel and lodging expenses. The number of treatment cycles needed to achieve pregnancy will, of course, determine the final cost.
A reduction in cost may be obtained by using "Natural Cycle IVF." This procedure does not employ ovulation enhancement; therefore the additional expense on the injections used for superovulation is eliminated. However, only one mature egg is usually obtained, and the pregnancy rate per cycle is therefore less for this method. A newer technique called "in vitro maturation" allows doctors to collect many immature eggs, and them mature them in the laboratory.